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BioMed Central Page 1 of 21 (page number not for citation purposes) Radiation Oncology Open Access Methodology On the performances of different IMRT treatment planning systems for selected paediatric cases Antonella Fogliata 1 , Giorgia Nicolini 1 , Markus Alber 3 , Mats Åsell 4 , Alessandro Clivio 1 , Barbara Dobler 2 , Malin Larsson 5 , Frank Lohr 2 , Friedlieb Lorenz 2 , Jan Muzik 3 , Martin Polednik 2 , Eugenio Vanetti 1 , Dirk Wolff 2 , Rolf Wyttenbach 6 and Luca Cozzi* 1 Address: 1 Oncology Institute of Southern Switzerland, Medical Physics Unit, Bellinzona, Switzerland, 2 Universitätsklinikum Mannheim, Klinik für Strahlentherapie und Radioonkologie, Mannheim, Germany, 3 Biomedical Physics, Radiooncology Dept, Uniklinik für Radioonkologie Tübingen, Tübingen, Germany, 4 Nucletron Scandinavia AB, Uppsala, Sweden, 5 RaySearch Laboratories, Stockholm, Sweden and 6 Ospedale Regionale Bellinzona e Valli, Radiology Dept, Bellinzona, Switzerland Email: Antonella Fogliata - afc@iosi.ch; Giorgia Nicolini - giorgia.nicolini@iosi.ch; Markus Alber - markus.alber@med.uni-tuebingen.de; Mats Åsell - mats.asell@se.nucletron.com; Alessandro Clivio - aclivio@iosi.ch; Barbara Dobler - Barbara.Dobler@klinik.uni-regensburg.de; Malin Larsson - malin.larsson@raysearchlabs.com; Frank Lohr - frank.lohr@radonk.ma.uni-heidelberg.de; Friedlieb Lorenz - friedlieb.lorenz@radonk.ma.uni-heidelberg.de; Jan Muzik - jan.muzik@med.uni-tuebingen.de; Martin Polednik - martin.polednik@radonk.ma.uni-heidelberg.de; Eugenio Vanetti - evanetti@iosi.ch; Dirk Wolff - dirk.wolff@radonk.ma.uni- heidelberg.de; Rolf Wyttenbach - rolf.wyttenbach@bluewin.ch; Luca Cozzi* - lucozzi@iosi.ch * Corresponding author Abstract Background: To evaluate the performance of seven different TPS (Treatment Planning Systems: Corvus, Eclipse, Hyperion, KonRad, Oncentra Masterplan, Pinnacle and PrecisePLAN) when intensity modulated (IMRT) plans are designed for paediatric tumours. Methods: Datasets (CT images and volumes of interest) of four patients were used to design IMRT plans. The tumour types were: one extraosseous, intrathoracic Ewing Sarcoma; one mediastinal Rhabdomyosarcoma; one metastatic Rhabdomyosarcoma of the anus; one Wilm's tumour of the left kidney with multiple liver metastases. Prescribed doses ranged from 18 to 54.4 Gy. To minimise variability, the same beam geometry and clinical goals were imposed on all systems for every patient. Results were analysed in terms of dose distributions and dose volume histograms. Results: For all patients, IMRT plans lead to acceptable treatments in terms of conformal avoidance since most of the dose objectives for Organs At Risk (OARs) were met, and the Conformity Index (averaged over all TPS and patients) ranged from 1.14 to 1.58 on primary target volumes and from 1.07 to 1.37 on boost volumes. The healthy tissue involvement was measured in terms of several parameters, and the average mean dose ranged from 4.6 to 13.7 Gy. A global scoring method was developed to evaluate plans according to their degree of success in meeting dose objectives (lower scores are better than higher ones). For OARs the range of scores was between 0.75 ± 0.15 (Eclipse) to 0.92 ± 0.18 (Pinnacle 3 with physical optimisation). For target volumes, the score ranged from 0.05 ± 0.05 (Pinnacle 3 with physical optimisation) to 0.16 ± 0.07 (Corvus). Conclusion: A set of complex paediatric cases presented a variety of individual treatment planning challenges. Despite the large spread of results, inverse planning systems offer promising results for IMRT delivery, hence widening the treatment strategies for this very sensitive class of patients. Published: 15 February 2007 Radiation Oncology 2007, 2:7 doi:10.1186/1748-717X-2-7 Received: 29 November 2006 Accepted: 15 February 2007 This article is available from: http://www.ro-journal.com/content/2/1/7 © 2007 Fogliata et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Radiation Oncology 2007, 2:7 http://www.ro-journal.com/content/2/1/7 Page 2 of 21 (page number not for citation purposes) Background Radiation Therapy is administered to approximately one- half of the children affected by oncological pathologies to manage their disease [1]. The choice of available radiation treatments includes intensity-modulated radiotherapy (IMRT) that should therefore be investigated in the challenging field of paediatric radio-oncology. IMRT has been proven, at least in planning studies, to improve conformal avoidance when compared to 3D conformal techniques (3DCRT) [2-7]. Improved dose distributions are generally expected to correlate with (significant) reduction of acute and late toxicity as already documented in paediatric radiation oncology by some authors, who reported low morbidity in children treated with IMRT [8-11]. As an example, in a cohort of 26 patients treated for medulloblastoma, the mean dose delivered to the auditory apparatus was 36.7 Gy for IMRT and 54.2 Gy for 3DCRT; 64% of the 3DCRT treated patients developed grade 3 to 4 hearing loss, compared to only 13% in the IMRT group [8]. Despite its potential, IMRT is not widely used in the paediatric field, and its introduction is significantly slower than for adults. Consequently, there is a substantial lack of knowledge on the late side effects of IMRT as pointed out in the review article of Rembielak [12]. The main lim- itation observed in this review is the publication of data of small series and short-term follow-up. In addition, the majority of studies investigated tumours located in the brain and CNS, with few other sites [8-10,13-15]. One of the major factors limiting the use of IMRT in paediatric oncology lies in the possible increase of radiation- induced secondary malignancies, caused mostly by the increased volume of patient receiving low dose levels. This effect derives from the generally increased number of fields entering from various angles and from a higher number of monitor units (MU) compared with 3DCRT, delivering higher leakage radiation estimated to be from 2 to 12 times higher than 3DCRT. However, this issue is controversial. Followill [16] showed that for 6 MV treatments the estimated likelihood of a fatal secondary cancer due to a 70 Gy treatment increased from 0.6% for wedged conventional treatment to 1.0% for IMRT, showing that 3DCRT is not significantly different from IMRT. Also Koshy [17] have found (in children treated for head-and- neck, brain, trunk, abdomen and pelvis) no significant differences in dose received by thyroid and breast glands when IMRT or 3DCRT were administered. Paediatric treatments are anyway delicate since enhanced radiation sensitivity is expected. Hall [18,19] showed that children are more sensitive than adults by a factor of 10; in addition, radiation scattered inside the patient is more significant in the small body of a child than in a larger adult body, and there is a genetic susceptibility of paediatric tissues to radiation-induced cancer. Therefore, there is a need of more clinical IMRT studies to assess the balance between the positive therapeutic effects and the risk of radiation- induced secondary malignancies. The present study aimed to address the problem of IMRT in paediatric radiation oncology from a different point of view. Assuming that research activity in treatment planning or at clinical level shall be promoted, it is important to analyse if the tools available for IMRT are adequate and effective. A comparative study was conducted, similar to a previous investigation on breast cancer [20], on the most commonly available Treatment Planning Systems (TPS) to assess their respective performance and their potential limits in planning IMRT for some paediatric indications that were chosen as difficult to be treated optimally with 3DCRT. The rationale to develop and report a study like the present is multifactorial and is mainly based on the following pillars. i) at present, very few studies, and probably none on paediatrics, exist addressing the issue of comparing different commercial planning systems for IMRT. The study on breast was the first published by this research group and aimed to prove (with a minimally acceptable set of five homogeneous patients) the adequacy of various TPS in terms of conformal avoidance, for a specific tumour side. Having proved that principle, it was felt necessary to expand the research on a different class of patients. ii) with the new study we aimed to address the usability of the commercial TPS on pathologies which are more complicate in nature, rarer and more challenging such as pediatric cases where treatment planning requires particular skills and it is bounded by dose-limiting constraints often severely different from the ones applied to adults. As men- tioned, literature is poor in this respect. iii) in the field of paediatrics there is a generally weak knowledge about IMRT and, to complicate the problem, the variety of indications is huge and, at the limit, every individual patient presents peculiarities (given by the physiological variability in the evolutionary age) prevent- ing easy generalisations. Therefore, rather than trying to identify one single pathology and a consistent cohort of patients, in the present study we preferred to identify a (small) group of complicate cases, one case per indica- tion, but all of them presenting specific planning challenges. On the other side, it was decided to limit the number of cases to present in order to minimise data pres- entation considering the results qualitatively sufficient to prove the aims. Radiation Oncology 2007, 2:7 http://www.ro-journal.com/content/2/1/7 Page 3 of 21 (page number not for citation purposes) iv) the study aimed at understanding if systems were keep- ing the reliability shown for breast also under conditions uncommon and distant from those generally used in IMRT planning and likely not tested in the development and qualification phases. The strategy described above, allowed testing IMRT capabilities of routinely available commercial TPS under a range of rather extreme (although rare) conditions. In this respect, the specific choice of indications, and the actual status of the selected case, does not limit or affect the potential of investigating complicate situations that could be used as templates for similar cases. Clinical questions (like outcome and toxicity) should be addressed in properly designed clinical trials and are not subjects of comparative planning studies. Methods Four paediatric patients, affected by different types of cancer, were chosen. The tumour types were: one extra osseous, intrathoracic Ewing Sarcoma; one mediastinal Rhabdomyosarcoma; one Rhabdomyosarcoma of the anus with intrapelvic, inguinal and osseous metastases; one Wilm's tumour of the left kidney with multiple liver metastases. In table 1 a summary of the diagnosis, dose prescriptions, and planning objectives (PObj) for organs at risk (OAR) is presented. For all cases except patient 4, the treatment was structured in two courses, with two different planning target volumes (PTV): PTV1 being the elective and PTV2 the boost volumes. The PObj concerning OARs refer mainly to the report of the National Cancer Institute [21,22]. To avoid scaling effects due to optimisation [20], dose was normalised to the mean PTV value. Datasets were distributed among participants in DICOM (CT images) and DICOM-RT (contours of volumes of interest – VOIs) format as defined at the reference centre (Bellinzona, Switzerland). Seven TPS with inverse planning capabilities were compared. Information on release used and main references for dose calculation and optimisation algorithms are reported in table 2. All TPS, except Hyperion, are commercial systems. Pinnacle 3 implemented two optimisation Table 1: Main characteristics of patients and treatment. Patient 1 Patient 2 Patient 3 Patient 4 Patient Male, 12 y.o. Female, 8 y.o. Female, 13 y.o. Female, 8 y.o. Diagnosis Ewing Sarcoma extraosseous, intrathoracic Rhabdomyosarcoma mediastinum, stage III Rhabdomyosarcoma anus. Metastasis lymphnodes intrapelvic, inguinal and osseous Wilm's tumour of the left kidney. (Multiple lung metastasis). Multiple liver metastasis Status After chemotherapy + surgery + chemotherapy After chemotherapy After chemotherapy After chemotherapy + left nefrectomy + chemo- radiotherapy for lung metastasis Radiotherapy dose prescription Total = 54.4 Gy, Total = 50.4 Gy, Total = 50.4 Gy, Total = 18 Gy, 1.6 Gy/fraction 1.8 Gy/fraction 1.8 Gy/fraction 1.2 Gy/fraction 2 fractions/day 1 fraction/day 1 fraction/day 1 fraction/day I course (PTV1) = 44.8 Gy I course (PTV1) = 45 Gy I course (PTV1) = 45 Gy II course(PTV2) = 9.6 Gy (boost, excludes surgical scar) II course (PTV2) = 5.4 Gy (boost) II course (PTV2) = 5.4 Gy (boost, excludes the two inguinal nodes regions) Target volumes PTV1 = 564 cm 3 PTV1 = 109 cm 3 PTV1 = 618 cm 3 PTV1 = 1234 cm 3 PTV2 = 549 cm 3 PTV2 = 72 cm 3 PTV2 = 193 cm 3 Organs at risk dose objectives Lung 1 < 15 Gy Lung 1 < 15 Gy Rectum 1 < 40 Gy Kidney 1 < 10 Gy Heart 1 < 30 Gy Heart 1 < 30 Gy Bladder 1 < 30 Gy Vertebra 1 < 20 Gy Vertebra 1 < 20 Gy Uterus 1 < 20 Gy Spinal cord 2 < 45 Gy Spinal cord 2 < 45 Gy Femural heads 1 < 20 Gy Beam arrangement 6 fields. (both courses) Gantry angles: 180, 165, 125, 90, 60, 340 7 fields. (both courses) Gantry angles: 0, 30, 100, 130, 230, 260, 330 I course: 7 fields. Gantry angles: 0, 51, 103, 154, 206, 257, 308 5 fields Gantry angles: 0, 72, 144, 216, 288 II course: 5 fields: Gantry angles: 0, 72, 125, 235, 288 1: mean dose; 2: maximum dose Radiation Oncology 2007, 2:7 http://www.ro-journal.com/content/2/1/7 Page 4 of 21 (page number not for citation purposes) methods: one related to physical quantities and the other to a combination of physical and 'biological' (Equivalent Uniform Dose, EUD) quantities and was therefore considered twice. Hyperion combined 'biological' optimisation with a Monte Carlo (MC) engine. All the other TPS have optimisation engines which rely on physical optimisation only and dose calculation was performed using either pencil beam (PB) or convolution/superposition algorithms such as the Collapsed Cone (CC) or the Aniso- tropic Analytical Algorithm (AAA) or MonteCarlo (MC). All TPS (except Eclipse and KonRad) supported only static segmental (step-and-shoot) IMRT; Eclipse plans in the present study used dynamic (sliding window) MLC sequencing. The number of intensity levels (IL) used by the static systems to discretise individual beam fluence was generally 10. For Corvus IL was set to 3, but it is an aperture based system with manual segment generation and inverse optimisation of the segment weights. For Hyperion, the segmentation process does not use ILs, rather a set of constraints such as segment size, dose per segment and total number of segments. For OMP and Pinnacle 3 the total number of segments, the segment size and the minimum MU per segment are the set parameters. A set of procedural guidelines was defined including spec- ifications of the PObj's to fulfil. Given the specifics of each TPS, the choice of numerical objectives translating the PObj into e.g. dose-volume constraints was not fixed. Also 'dummy' volumes, steering the optimisation engines to improve results, were allowed to compare the 'best' plans under given conditions [20]. To avoid variability in the results due to different beam arrangements, the number of fields and the beam geometry were fixed. Bolus was allowed if required. All plans were designed for 6 MV photon beams using multileaf collimators with 80 or 120 leaves. The three following objectives should be achieved: i) target coverage (min. dose 90%, max. dose 107%), ii) OAR sparing to at least the limits stated in table 1, iii) sparing of healthy tissue (HTis, defined as the CT dataset patient volume minus the volume of the largest target). The dose limits on OARs and HTis were strengthened by the additional requirement to minimise the volumes involved. No specific model for the calculation of the risk of secondary cancer induction was applied because of no consensus about their value. Hence, the analysis was lim- ited to the evaluation of physical quantities. Every TPS was required, using whichever method, to minimise the involvement of HTis. The dose constraints reported in table 1 are specific to paediatric cases and more restrictive than the corresponding for adults and all were derived from specific literature publications. The cases and indications were selected in order to obtain a minimal set of complicate planning situations with specific challenges to resolve to test TPS capabilities. For patient 1 the main challenges were: the target was adjacent to the spinal cord, partially inside the lung with a long scar (about 5 cm) generating a secondary target volume, separated from the main one, smaller in volume and located along the thoracic wall but requiring simultaneous irradiation. Complementary to these geometrical conditions, there is a generic need, in paediatrics, to generate rather symmetric irradiation of the body (in this case the vertebrae) to prevent potential risks of asymmetric growth. For patient 2, the location of the target in the mediastinum would be relevant in terms of large dose baths in the lung (and eventually breast) regions. For patient 3, the target volume was divided into three unconnected regions (the anal volume and the two inguinal node regions) with organs at risk generally posi- tioned in-between the three targets (as uterus, bladder and rectum). For patient 4, the target volume was given by the entire liver and the main organ at risk was the right kidney with a low tolerance, located proximal/adjacent to the target. The sparing of this kidney had a very high priority since the patient underwent left nephrectomy. Table 2: TPS characteristics and references TPS, release Calculation alg. Optimisation alg. References Corvus, 5.0 Corvus Pencil beam Simulated annealing [25] Eclipse, 7.5.14.3 Eclipse Anisotropic Analytical Algorithm (AAA) Conjugated gradient [26,27,28,29,30,31,32] Hyperion, 2.1.4 Hyperion Monte Carlo Conjugate gradient [33,34,35,36] KonRad, 2.2.18 KonRad Pencil beam Conjugate gradient [37,38] Oncentra Master Plan, 1.5 OMP Pencil beam Conjugate gradient [39,40] Pinnacle 3 EUD, 7.4f PinnEUD Collapsed cone Gradient based, sequential quadratic programming [41,42,43,44] Pinnacle 3 Phys, 7.4f PinnPhy Collapsed cone Gradient based, sequential quadratic programming [42,45,46] PrecisePLAN, 2.03 Precise Pencil beam Cimmino [47] Radiation Oncology 2007, 2:7 http://www.ro-journal.com/content/2/1/7 Page 5 of 21 (page number not for citation purposes) For patients 1, 2 and 3, treatment plans were generated for two separate treatment courses and for the complete treatment, as the sum of partial plans according to dose prescriptions reported in table 1. In no case was the concept of simultaneous integrated boost (SIB) applied. All TPS, except KonRad (in the implementation used although in principle possible), were able to produce the summed plan; for KonRad, only the mean doses to the VOIs were used in the analysis of the entire treatment since the sum of the mean doses in a VOI is equal to the mean dose of the summed plan in that VOI. The maximum point dose reported for the entire treatment for KonRad plans was recorded as the sum of the two separate plan maximum doses, even if this value could be overestimated (does not take into account the actual location of the individual plan maxima). The TPS can be divided into two families: a first, where the two courses are planned independently (Corvus, Eclipse, KonRad) and a second, where the plans for the second course are optimised based upon knowledge of the dose distribution already "accumulated" in the first course (Hyperion, OMP, Pinnacle 3 , Precise). In principle, Kon- Rad could belong to the second family, but in the present study it was not the case. The number of MU/Gy has been investigated since in pediatric radiation oncology this is a highly relevant issue in terms of possible induction of secondary malignancies. MU values from the different TPS were normalised to a virtual output of 1 Gy for 100 MU, 10 × 10 cm 2 field, SSD = 90 cm and 10 cm depth (isocentre). Evaluation tools The analysis was based on isodose distributions and on physical DVHs of PTVs, OARs and HTis. From DVHs, the following parameters were compared: D x (the dose received by x% of the volume); V y (the volume receiving at least y dose (in percentage of the prescribed dose or in Gy)); mean dose; maximum and minimum point doses; maximum and minimum significant doses defined as D 1% and D 99% respectively, and standard deviation (SD). For HTis we also report the volume receiving at least 10 Gy normalised to the elective PTV (nV 10 Gy ) to assess the relative extent of irradiation at low dose levels. A Conformity Index (CI) was defined for each PTV and treatment course as the ratio of the volume receiving 90% of the dose prescribed for this specific volume and the PTV itself. Finally, to introduce a plan ranking, a 'goodness' parameter was defined for OARs (including HTis) and PTVs: where the sum is extended to the number of evaluated OARs or PTVs (nOAR or nPTV), Val plan is, for each chosen parameter (one for each VOI, e.g. mean dose to the lung), the value found after DVH analysis of the sum plans; PObj are the relative plan objectives as in table 1. For HTis the V 10 Gy parameter was chosen and, as PObj, the mean value of the parameter over all the TPS for each patient was used. The sum is normalised to the number of OARs or PTVs used. For PTVs, the Score analyses the fraction of volume receiving less than the 90% or more than the 107% of the prescribed dose in the first course plan and, for the boost, it analyses the data of the summed plans. In this way, the TPS of the second family are not penalised. According to the definition, the Score should be as low as possible and smaller than 1. In the evaluation phase, plans were considered as acceptable if respecting (or minimally violating) the planning objectives and plans with lower scores were considered preferable. Results Figures 1 and 2 present, for a representative CT image, the dose distribution for the four patients, the PTVs shown in black and some relevant OARs in white. Data are reported for the total plan (i.e. sum of plans for PTV1 and PTV2 for the first 3 patients). Figures 3, 4, 5, 6 show the DVH of PTV2 (PTV for patient 4) and for the involved OAR for the total treatment for each patient and for all TPS. From the dose distribution figures it is possible to qualitatively appraise the different degrees of conformal avoidance, the extension of the low dose areas, the degree of uniformity of doses within the PTVs and the potential presence of hot spots. Table 3 presents for all OARs, PTVs and HTis, for all patients and for the most relevant parameters, the PObj and the average values computed over all the TPS. Uncer- tainty is given at one standard deviation (SD). Data for OARs are given for the total plans while for the first three patients PTV data are given for the two courses separately and, for PTV2 only, also for the total treatment (PTV2 (total)). Score OAR nOAR Val PObj plan OAR n n ()= () () ∑ 1 1 Score PTV nPTV Val PObj plan PTV n n ()= () () ∑ 1 2 Radiation Oncology 2007, 2:7 http://www.ro-journal.com/content/2/1/7 Page 6 of 21 (page number not for citation purposes) Table 4 reports the averages, computed over the four patients and over all the PTVs (analysing the single plans), of the parameters expressing the degree of target coverage for all the TPS. For D 1% and D 99% the data are reported as percentage of the prescribed dose for each PTV. Tables 5, 6, 7, 8 present for each patient the same parameters with the findings for each TPS. In all Figures, the KonRad data are shown only for the last patient while in the tables, the results are shown only for the mean and maximum point doses for the summed plans since dose distributions could not be summed up, as described above. Target coverage For PTV1 and PTV2 the analysis was conducted also for the DVHs of the separate courses. In this case, the results for the TPS of the second family, are poorer for the boost for the reason described in the methods (CI, in some cases, e.g. Patient 1, is even lower than 1). This feature also affects the results in table 4 which shall therefore be considered with some caution for Hyperion, OMP, Pinnacle 3 and Precise (e.g. CI). Analysing the data, it is possible to notice certain uniformity of results for most of the parameters. In some cases, these are all sub-optimally fitting the objectives and prove the difficulty of all the TPS to achieve high conformality on targets when, as for paediatric cases, the fulfilment of dose constraints for OARs and HTis is emphasised. The risk of under dosage of the PTV is common to all TPS (e.g., from table 4 and complementary tables, V 90% and D 99% present large deviations from the ideal objective values). For Patient 1, PinnEUD showed a large over dosage of the PTV2 (total) where V 107% = 23% (table 5); this is signifi- Dose distributions of the summed plan (overall treatment) for Patient 1 and Patient 2Figure 1 Dose distributions of the summed plan (overall treatment) for Patient 1 and Patient 2. Eclipse Corvus HyperionMC OMP PinnaclePHY PinnacleEUD Precise 16.3 Gy (30% of 54.4 Gy) 27.2 Gy (50% of 54.4 Gy) 38.1 Gy (70% of 54.4 Gy) 44.8 Gy (prescr. dose PTV1) 54.4 Gy (total prescr. dose) 59.8 Gy (110% of 54.4 Gy) Patient 1 Corvus Eclipse HyperionMC OMP PinnaclePHY PinnacleEUD Precise 15.1 Gy (30% of 50.4 Gy) 25.2 Gy (50% of 50.4 Gy) 35.3 Gy (70% of 50.4 Gy) 45.0 Gy (prescr. dose PTV1) 50.4 Gy (total prescr. dose) 55.4 Gy (110% of 50.4 Gy) Patient 2 Radiation Oncology 2007, 2:7 http://www.ro-journal.com/content/2/1/7 Page 7 of 21 (page number not for citation purposes) cantly different from all other cases. For the two most complicated cases, OMP showed the best values for patient 1 (difficult for the small superficial scar volume), and Hyperion for patient 3 (difficult for the positioning of the three PTVs with particularly radiosensitive OARs in between). Organs at risk Given the different anatomical location of the tumours and the different PObj for each OAR, each of the 4 patients is considered separately. Patient 1: the objective selected for the vertebra (that was partially included in the target) was respected only by OMP (table 5) (and almost by Hyperion). Doses larger than 25 Gy were observed for Precise and PinnPhy. The PObj for spinal cord was only not reached by PinnPhy (looking at the maximum point dose) but the limit was not violated if D 1% is considered. All TPS respected the constraint on the mean dose to contra lateral lung and Hyperion was the only TPS to (almost) keep the mean dose to the uninvolved omolateral lung below 15 Gy. KonRad was the only TPS not able to reach the objective for the heart. Averaging over the TPS, the PObj were not respected for the vertebra and for the uninvolved omolateral lung (table 3). Patient 2: PObj's were respected by all TPS, with the minor exception of PinnPhy where the mean dose to the vertebra was 20.8 Gy instead of 20 Gy. Patient 3: From table 3, on average, all objectives were respected. For the mean uterus dose of 20 Gy, Precise (21.5 Gy), KonRad (20.5 Gy) and OMP (20.5 Gy) show minor violations. Bladder and Rectum did not cause any problems (OMP reached the limit on the bladder; Hyper- Dose distributions of the summed plan (overall treatment) for Patient 3 and Patient 4Figure 2 Dose distributions of the summed plan (overall treatment) for Patient 3 and Patient 4. Precise Corvus Eclipse HyperionMC OMP PinnaclePHY PinnacleEUD 15.1 Gy (30% of 50.4 Gy) 25.2 Gy (50% of 50.4 Gy) 35.3 Gy (70% of 50.4 Gy) 45.0 Gy (prescr. dose PTV1) 50.4 Gy (total prescr. dose) 55.4 Gy (110% of 50.4 Gy) 5.4 Gy (30% of 18 Gy) 9.0 Gy (50% of 18 Gy) 12.6 Gy (70% of 18 Gy) 16.2 Gy (90% of 18 Gy) 18.0 Gy (total prescr. dose) 19.8 Gy (110% of 18 Gy) Corvus HyperionMC PinnaclePHY Precise Eclipse OMP PinnacleEUD KonRad Patient 3 Patient 4 Radiation Oncology 2007, 2:7 http://www.ro-journal.com/content/2/1/7 Page 8 of 21 (page number not for citation purposes) Dose-Volume Histograms for targets and all organs at risk for Patient 1Figure 3 Dose-Volume Histograms for targets and all organs at risk for Patient 1. Data refer to the complete treatment. Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 PTV2 Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 1020 30405060 Volume [%] 0 20 40 60 80 100 120 PTV1-PTV2 Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Vertebra Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 1020 30405060 Volume [%] 0 20 40 60 80 100 120 Spinal Cord Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Right Lung Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 1020 30405060 Volume [%] 0 20 40 60 80 100 120 Left uninvolved Lung Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Heart Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 1020 30405060 Volume [%] 0 20 40 60 80 100 120 Healthy Tissue Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Radiation Oncology 2007, 2:7 http://www.ro-journal.com/content/2/1/7 Page 9 of 21 (page number not for citation purposes) Dose-Volume Histograms for targets and all organs at risk for Patient 2Figure 4 Dose-Volume Histograms for targets and all organs at risk for Patient 2. Data refer to the complete treatment. Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 PTV2 Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 PTV1-PTV2 Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Vertebra Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Spinal Cord Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Right Lung Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Left Lung Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Heart Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Healthy Tissue Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Radiation Oncology 2007, 2:7 http://www.ro-journal.com/content/2/1/7 Page 10 of 21 (page number not for citation purposes) Dose-Volume Histograms for targets and all organs at risk for Patient 3Figure 5 Dose-Volume Histograms for targets and all organs at risk for Patient 3. Data refer to the complete treatment. Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 PTV2 Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 PTV1-PTV2 Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Uterus Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Rectum Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Bladder Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Right Femur Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Left Femur Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Dose [Gy] 0 102030405060 Volume [%] 0 20 40 60 80 100 120 Healthy Tissue Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise Corvus Eclipse Hyperion OMP Pinnacle EUD Pinnacle PHY Precise [...]... final dose calculation engines Therefore no true factorisation process is possible to limit a comparison of performances to the optimisation phase On the other side, the impact of dose calculation algorithms in some range of clinical conditions is object of independent evaluations in more standard conditions (e.g Knöös [24]) and results can be likely generalised to IMRT The issue of MU was here addressed... defined volumes of interest 13 MA performed planning on Masterplan ML performed planning on Pinnacle 14 AF and GN performed planning on Eclipse 15 JM and MA performed planning on Hyperion BD, FL and FL performed planning on Konrad 16 17 MP and FL performed planning on PrecisePlan 18 BD, DW and FL performed planning on Corvus 19 AC, EV, AF and GN coordinated and carried out data collection, program development... fall-off of doses at distal edge of the Bragg's peaks) Some studies appeared and potentials are encouraging [23] even if care should be put on the proton technique as pointed out by Hall [19] since, for example, passive scattering modalities could increase the neutron contaminations and the "MU" needed to delivery the prescribed dose with potential impact on the probability of secondary cancer induction... identify proper indications but, in the absence of generally available proton facilities, or in the presence of severe logistic limits, photons based IMRT could be anyway considered as a valid approach The stability or sensitivity of different TPS against variations in the planning objectives was not considered as part of the study because considered as beyond the purposes of the study and would deserve... response of the main commercial systems to paediatric IMRT is addressed by this study Considering target coverage and limiting the discussion to the second family of TPS, significantly heterogeneous dose distributions were observed for the targets in the boost courses Considering as an example (without any implication of merit) PinnEUD and patient 1, for PTV2, the volume receiving less than 90% of the. .. analysing the MU/Gy for all TPSs, even if no effort was put in the application of models to estimate secondary cancer induction from the observed 3D dose distributions This is an important aspect of paediatric radiation oncology, and detailed descriptions of linac head, shielding, beam spectra, neutron and electron contamination should be modelled in the dose calculation algorithms This was felt to be beyond... explicitly included in the list of organs at risk and for patient 3 the same applies to ovaries Concerning breast, in this case the issue is not heavy involvement of the glands (i.e irradiation at high dose levels) but rather the dose bath and the potential for secondary cancer induction In the absence of reliable models to predict the risk of secondary cancers (unfortunately all the studies that appeared... three-dimensional treatment planning Med Phys 1993, 20:311-318 Bortfeld T, Bürkelbach J, Schlegel W: Three-dimensional solution of the inverse problem in conformation therapy In Advanced Radiation Therapy Tumor Response Monitoring and Treatment Planning Edited by: Breit Springer Verlag, Berlin; 1992:503-508 Gustafsson A, Lind BK, Brahme A: A generalized pencil beam algorithm for optimization of radiation therapy... normal codes of practice (with also potential financial implication depending on the reimbursement schemes) As proven in many other IMRT studies, the degree of conformal avoidance with photon based IMRT is not perfect and trade-offs should be considered for complex situations This proves to be particularly important in the case of paediatric oncology due to low tolerances, small distances among organs,... only one (e.g MC) reliable engine In fact, for most of the TPS this is impossible because, if the optimisation is performed using pencil beam algorithms (eventually simplified for speed reasons), the multileaf segmentation http://www.ro-journal.com/content/2/1/7 engines quite often include some consideration of the head scattered radiation from the linac head and this is intimately connected with the . 1 of 21 (page number not for citation purposes) Radiation Oncology Open Access Methodology On the performances of different IMRT treatment planning systems for selected paediatric cases Antonella. calculation engines. Therefore no true factorisation process is possible to limit a comparison of performances to the optimisation phase. On the other side, the impact of dose calculation algorithms. involvement of the glands (i.e. irradiation at high dose levels) but rather the dose bath and the potential for secondary cancer induction. In the absence of reliable models to predict the risk of secondary